A series of direct-acting alkylating and acylating compounds will be studied to determine whether their carcinogenic potency in the respiratory tract is related to their chemical reactivity. Relatively short but intense inhalation exposures of Sprague Dawley rats will be carried out, with the concentration of the compounds adjusted to reflect their relative chemical reactivities. In a series of parallel in vitro studies, the same chemicals will be examined for their abilty to effect transformation and mutagenesis in mammalian cell systems.